Biological complexity: wet noodle proteins (Introduction)

by David Turell , Friday, January 20, 2017, 20:41 (2864 days ago) @ David Turell

The past teaching was that all proteins functioned only of they were fixed in amino acid sequences and folded in certain required ways. Not true. There are very important proteins that are as floppy as wet noodles and they have very important functions:

https://www.quantamagazine.org/20170118-disordered-proteins/?utm_source=Quanta+Magazine...

"Proteins are chains of strung-together amino acids, and recent studies estimate that up to half of the total amino acid sequence that makes up proteins in humans doesn’t fold into a distinct shape. (While some of the proteins that make up this total are unstructured from end to end, others contain long unstructured regions side-by-side with structured ones.) “Partly, people didn’t realize how big that number was, and that’s why they ignored it,” said Julie Forman-Kay, a biochemist at the Hospital for Sick Children and the University of Toronto. “And partly they just didn’t know what to think of it.”

"This fluidity — dubbed “intrinsic disorder” — endows proteins with a set of superpowers that structured proteins don’t have. Folded proteins tend to bind to their targets firmly, like a key in a lock, at just one or two spots, but their more stretched-out wiggly cousins are like molecular Velcro, attaching lightly at multiple locations and releasing with ease. This quick-on-quick-off binding’s effect in the cell is huge: It allows intrinsically disordered proteins — or IDPs, for short — to receive and respond to a slew of molecular messages simultaneously or in rapid succession, essentially positioning them to serve as cellular messaging hubs, integrating these multiple signals and switching them on and off in response to changes in the cell’s environment and to keep cellular processes ticking along as they should.

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" Through their signaling prowess, IDPs help regulate the gas and brake pedals for producing proteins from the DNA code, according to evidence that has accumulated over the past decade, as well as the process by which cells divide. IDPs may also provide cues that allow cells to take on traits specific to different tissues or parts of the body. In other words, they may somehow help make a blood cell a blood cell and a muscle cell a muscle cell.

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"Protein disorder occurs along a continuum. At one end of the spectrum lie proteins like p21, which fold on contact with other proteins. At the other end are ones that remain limp and floppy, like wet noodle strands, never taking on a shape. Researchers still don’t know how this range corresponds to their versatile functions, but being more like a string than like a lump with keyholes means that a protein can make many contacts with other molecules to regulate the network of signals that drives the cell. “You have all these on-off switches for all kinds of functions,” said Dunker.

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"When they examined a database of around 5,000 human proteins, they found that most unstructured proteins were expressed in small quantities and quickly destroyed after they had done their job.

"The reason cells regulate their production so tightly and make sure they turn over so quickly is that IDPs pack a huge punch, Babu said. Having too many would be like having a glut of upper management  — with too many people shouting commands, productivity grinds to a halt. Extend that logic to a cell, though, and things can get ugly: Because IDPs regulate how different components of the cell communicate with one another, having extra copies floating around could leave them sending signals that shouldn’t get sent. “These proteins are so dangerous that you can’t afford not to regulate them,” Babu said.

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"As they continue to explore what disordered proteins do inside the cell, researchers are also pursuing basic questions about how disordered proteins work. If a protein has both disordered and ordered regions, how do the two interact? How did the evolution of disordered proteins differ from that of folded ones? Also, how do molecules figure out where to attach on disordered proteins? Even though both computer analysis and experimental lab tools for probing IDPs have improved over the past five years, studying them directly in a living cell remains a challenge, Wright said.

"Researchers also want to explore how disordered proteins contribute to disease. Most drugs are designed to interfere with a specific disease pathway by elbowing their way into important spots inside the cell. But researchers have only begun to target IDPs."

Comment: This presents a much higher level of cellular complexity than was ever imagined. How much complexity in biology has to be demonstrated before the decision is obvious that it requires creation by a planning mind?